Significance HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. Objective This study should determine if immunzation at distant mucosal sites can result in vaginal anti-SIV immune responses and whether the mucosa adjuvant cholera toxin (CT) was useful for this pupose. Results Two rhesus macaques were orally immunized with CT mixed with 1000ug of SIVp55 and 2 animals were orally immunized with CT mixed with 250ug of SIVp55. The animals immunized with CT and high dose antigen made strong systemic immune responses to P55 including antibody, T cell proliferative and T cell cytokine responses to P55. The immune responses in the animal immunized with low dose P55 were weak. Significant levels of anti-p55 IgA antibodies were found in the rectal secretions but not in the vaginal secretions of these animals. Four rhesus macaques were intranasally immunized with 100ug CT mixed with 200ug of SIVp55 and 2 animals were intranasally immunized with 10ug CT mixed with 250ug of SIVp55. The animals immunized with 10ug CT made strong systemic immune responses to P55 including antibody, T cell proliferative and T cell cytokine responses to P55. Significant levels of anti-p55 IgA antibodies were found in the rectal secretions and in the vaginal secretions of these animals. This study demonstartes that the mucosal adjuvant CT is effective in rhesus macaques. In addition, it is now clear that oral immunization is not an effective method for generating mucosal immune responses in the vagina and that intranasal immunization is an excellent route of immunzartion for elicitng vaginal immunity. Future Directions Test other vaccine preparations by intranasal route. KEYWORDS mucosal immunity, intranasal immunization, SIV antigens;